Proximal and Distal Nerve Crush Injury in a Rat Model: An Evaluation of Motor Recovery, Nerve Histology, and Spinal Cord Microgliosis
James M Kerns, PhD; Kyle J MacGillis, MD; Sarah Schram, BS; Donald Chuang, MD; Greg Schmidt, BS; Daniel Kielminski, BS; Andrew Ormseth, BS; Raman Michael, BS; Amit Parekh, MD; Feroz Osmani, MD; Jeffrey Loeb, MD, PhD;Mark Gonzalez, MD, PhD
University of Illinois at Chicago
Introduction: There is both clinical and experimental evidence that nerve lesions can differ in response and recovery based upon the distance from the cell body. A rat sciatic nerve crush model is well suited to test this hypothesis.
Materials and Methods: Forty-one rats were divided between two groups: the left side received either a proximal crush at the sciatic notch or a distal crush at the knee; the right side was an unoperated control. Behavioral evaluation using the extensor postural thrust test was performed at baseline and then again at weekly intervals. After selected intervals (1, 2, 5 or 10 weeks), the rats were anesthetized for an intracardiac perfusion with paraformaldehyde. The tissues (spinal cord and nerves) were harvested and postfixed for qualitative nerve histology (paraffin sections and trichrome stain) or quantitative microglial inflammatory analysis (frozen sections and Iba1 immunocytochemistry quantified using Metamorph image analysis software).
Results: Both the proximal and distal crush injuries produced significant reduction in motor function (percent motor deficit) following the crush lesion; the distal crush injury rats recovered motor strength faster since the lesion was 30mm closer to the motor target. Both groups eventually returned to preoperative/baseline function by 10 weeks. Upon examination of nerve histology distal to the crush lesion site, there was evidence of residual Wallerian degeneration profiles, decreasing by 10 weeks. Excellent axonal regeneration and remyelination was evident in both recovery groups. However, no histological differences between the proximal and distal nerve crush groups were observed. Immunocytochemistry showed the microglial response around affected motoneurons was robust for both lesion groups at one week postoperative; at two weeks the response was reduced in the distal lesion group while remaining high in the proximal lesion group.
Conclusions: Peripheral nerve injuries (anonotmesis) cause a local response and spinal cord insult characterized by neuroinflammation involving the microglial cells. The role of the microgliosis around injured neurons does not appear to be associated with cell death in these mild crush lesions, but is sustained in the slightly more severe proximal lesions such that full functional recovery is eventually attained for both lesion groups. Future studies could examine neuromuscular junctions in the leg muscles, more severe lesions, greater intervening distances, and other spinal cord changes.
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